Used alongside clinical variables, molecular prognostic signatures can identify postmenopausal women with ER+, HER2-negative breast cancer for whom extended endocrine therapy is not appropriate, according to findings from an analysis of 10-year recurrence data among patients participating in the TransATAC clinical trial, which were presented at the 2016 San Antonio Breast Cancer Symposium.1

“This was a unique cohort with well-annotated samples, mature clinical outcome and prognostic information for 6 signatures,” reported Ivana Sestak, PhD, of the Centre for Cancer Prevention, Queen Mary University of London, England.

It is important to incorporate clinical variables into prognostic assessments rather than to depend on molecular signatures alone, she emphasized.

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A growing list of multigene expression panels are designed to offer prognostic insight into hormone receptor (HR)-positive breast cancer in patients treated with endocrine therapy, Dr Sestak said.

The authors evaluated the prognostic performance of 6 different signatures for distant recurrence among 818 postmenopausal women with ER+, HER2-negative breast cancer, and identified the added prognostic value of signatures over clinical factors. Patients had undergone 5 years of tamoxifen or anastrozole therapy without chemotherapy.

The primary study endpoint was distant disease recurrence.

The researchers studied outcome associations with the following prognostic signatures: Clinical Treatment Score (CTS; based on nodal status, grade, tumor size, treatment regimen and patient age), immunohistochemical markers (IHC4; ER, PR, and HER2 status, Ki67 levels), Oncotype Recurrence Score (RS; 21 genes in the estrogen, proliferation, invasion, and HER2 pathways), Breast Cancer Index (BCI; H/I and 5 proliferation genes), Prosigna (ROR; 46 genes, proliferation score, tumor size), and EndoPredict (EPclin; 12 proliferation, differentiation, and estrogen genes plus nodal status and tumor size).

Of the tested signatures, CTS, ROR, and EPclin included clinical variables like nodal status, grade, and tumor size.

At a median follow-up of 10 years, all of the tested prognostic signatures proved to be “good predictors” of disease recurrence during years 1-10, identifying patients with node-negative disease and low risk of distant recurrence, for whom the value of chemotherapy was limited, Dr Sestak said.

For patients with node-positive disease, ROP/EPclin identified patients with low distant-recurrence risk, for whom chemotherapy is of limited value, she said.

For predicting recurrence during years 5 to 10 among patients with node-negative disease, “BCI, ROR, and EPclin were good predictors for late distant recurrence”—patients for whom extended endocrine therapy is unjustified, she reported.

“For node-positive, ROR/EPclin identified patients at low risk for late distant recurrence, for whom extended endocrine therapy is not justified,” she said.

Each of the 5 signatures with gene expression components improved the prognostic value of clinical variables (CTS); ROR and BCI offered the largest prognostic improvements over CTS alone (74.5% and 70.8% improvement over CTS alone, respectively), whereas Oncotype’s RS score only improved CTA prognostication by 33.3%.

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It was important not to eschew clinical variables in interpreting molecular risk signatures, Dr Sestak reiterated.

She declined to state whether a particular signature seemed to work best overall for node-negative or node-positive patient populations.


  1. Sestak I, Buus R, Cuzick J, et al. Comprehensive comparison of prognostic signatures for breast cancer in TransATAC. Paper presented at: 39th San Antonio Breast Cancer Symposium; Dec 2016; San Antonio, TX.